This competitive renewal application requests continued support for the Center for Education and Drug Abuse Research (CEDAR), a 20-year prospective investigation of 1,000 families, as presently completing its second period of funding. Families are ascertained on the basis of proband father who has either (1) substance use disorder (n=450) (SUD), (2) non-SUD non-psychiatric disorder (N=350) or, (3) Axis 1 non-SUD psychiatric disorder (N=100), and where there is a biological son of daughter (index subject) who is between 10-12 years of age. To control for project intervention effects, 100 SUD families are enrolled but not studied until terminal evaluation. Following baseline evaluation, the index subject and, where present, the next younger siblings are studied over a 20-year period until they attain age 30. In the course of multiple follow-up evaluations, the children are tracked from the stage of no drug use to drug use to substance use disorder (SUD) and correlated outcomes tracked from the stage of no drug use to drug use to substance use disorder (SUD) and correlated outcomes tracked from the stage of no drug use to drug use to substance use disorder (SUD) and correlated outcomes tracked from the stage of no drug use to substance use disorder (SUD) and correlated outcomes (psychopathology, crime, STD, etc.). At baseline, a total of 1,404 subjects will be enrolled with an estimated 1,106 (psychopathology, crime, STD, etc.). At baseline, a total of 1,404 subjects will be enrolled with an estimated 1,106 subjects available at final follow- up (age 30). The other siblings, the proband father and his spouse, as well as their first degree relatives, are also characterized with respect to psychiatric and psychosocial functioning. The overarching aim of CEDAR is to identify the factors associated with the liability to SUD in the context of ontogenetic progression from the period of late childhood through the maximum period of risk. Subjects undergo intensive biobehavioral and psychiatric measurement along with extensive documentation of environment characteristics (family, peers, school, neighborhood). The determinants and characteristics of person-environment interactions that contribute to SUD liability and outcome will thus be determined. From such informational empirically based selective preventions can be developed that target specific facets of SUD liability characteristics.